Timing of interventions to control neuronal chloride elevation in a model of neonatal seizures after hippocampal injury

The present age-specific group studies demonstrate that after OGD, NKCC1 transport activity significantly contributes to progressive [Cl^-]_i accumulation, depolarizing action of GABA, and delayed onset of ILDs. In this neonatal model of neuronal injury and ILDs, earlier treatment with bumetanide alone more efficiently recovered control baseline [Cl^-]_i and depressed epileptiform discharges. However, there was no time dependency to the anti-ictal efficacy of the combination of phenobarbital and bumetanide. These in vitro results suggest that after perinatal injury, early pre-emptive treatment with phenobarbital plus bumetanide would be as efficacious as late treatment after seizures are manifest.